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Concurrent induction of T-cell activation and apoptosis of osteosarcoma cells by adenovirus-mediated B7-1/Fas chimeric gene transfer

Cancer Gene Therapy volume 10, pages 717–725 (2003)Cite this article

Abstract

To establish an effective B7-based gene therapy against osteosarcoma, we transferred B7-1/Fas chimeric gene adenovirally into poorly immunogenic osteosarcoma cells. We found that adenovirus-mediated rat B7-1/Fas gene transfer induced (i) expression of rat B7-1/Fas chimeric molecules in osteosarcoma cells, (ii) activation of murine T cells, (iii) apoptosis of murine osteosarcoma cells in the presence of anti-rat B7-1 mAb in vitro, and (iv) therapeutic effects more prominently than B7-1 gene transfer on the development of pulmonary metastasis and survival of mice. These findings collectively support the therapeutic value of adenovirus-mediated B7-1/Fas gene transfer on poorly immunogenic osteosarcoma, which is resistant to a treatment protocol using transduction of B7-1 alone.

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Acknowledgements

We thank Drs Takafumi Ueda, Hirofumi Hamada, and Jeffrey A Bluestone for the kind donation of LM8 cells, 293-CrmA cells, and anti-CD3 mAb, respectively. We also thank M Kaya for technical assistance. This study was supported by the Grant-in-Aid provided by the Ministry of Education, Science, Sports, and Culture of Japan (Grant number: 11307026).

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Authors and Affiliations

  1. Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine, Sapporo, Japan

    Hideki Tsuji, Satoshi Kawaguchi, Takuro Wada, Satoshi Nagoya & Toshihiko Yamashita

  2. Division of Molecular Immunology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan

    Hideki Tsuji, Manabu Inobe & Toshimitsu Uede

  3. Department of Immunology, Juntendo University School of Medicine, Tokyo, Japan

    Hideo Yagita & Ko Okumura

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  1. Hideki Tsuji
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Correspondence to Hideki Tsuji.

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Tsuji, H., Kawaguchi, S., Wada, T. et al. Concurrent induction of T-cell activation and apoptosis of osteosarcoma cells by adenovirus-mediated B7-1/Fas chimeric gene transfer. Cancer Gene Ther 10, 717–725 (2003). https://doi.org/10.1038/sj.cgt.7700624

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